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Biomedical subjects

P Franco

Publications and source records attributed to P Franco.

At least 91 records · Page 5Linked to original sources
PubMed1990

Influence of growth hormone on the immunosuppressive effect of prednisolone in mice.

Growth hormone can be used to counteract some catabolic effects of long-term administration of glucocorticoids, such as impairment of growth in children and osteoporosis. However, owing to its immunostimulatory properties the hormone may counteract the effect of glucocorticoids on the immune system. To investigate this question we administered different doses of hGH (4, 8, 40 IU/kg) to C57/Bl/6J mice treated for two days with prednisolone, and evaluated thymus and spleen parameters and natural killer activity. Growth hormone at the dose of 4 and 8 IU/kg reversed prednisolone-induced reduction of spleen and thymus weight and cellularity, whereas the highest dose showed to be immunosuppressive in itself. Two days after treatment withdrawal, a recovery of spleen parameters was evident, whereas the thymus was still suppressed by preceding prednisolone or hGH (40 IU/kg) treatments. The pattern of natural killer activity displayed by the splenocytes resembled that present under treatment. In a second experiment prednisolone, administered for 10 days, drastically reduced the number of viable spleen and thymus cells as well as the relative spleen and thymus weights, an effect reversed by concomitant administration of hGH (0.8, 4, 8 IU/kg). Natural killer activity, which was significantly depressed by prednisolone, was restored by the intermediate GH dose only. The 8 IU/kg GH dose was immunosuppressive in itself.

Analysis of Variance↗
PubMed1990

[Thyroid cancer and its incidence in nodular thyroid diseases: our experience].

The authors report their experience with 453 cases of thyroid nodules observed over a period of 5 years. The intention was to determine the incidence of malignant lesions. A female prevalence of the nodular pathology was clearly evident (7.2%), with a maximum incidence between the 3rd and 6th decade. Among malignant tumors (14.2%) the following histologic types were most frequently found: papillary adenocarcinoma (5.7%), follicular adenocarcinoma (2.7%), occult cancer (2.7%), anaplastic cancer (2.3%). Up to the 4th decade female prevalence was clearly evident (Max in the 3rd decade; F/M ratio = 6.5); then an increased male incidence was registered bringing to a reduction of the F/M ratio (1.5 in the 5th and 6th decade) and to its inversion in the 7th decade (M/F = 1.25).

Adenocarcinoma↗
PubMed1989

Assimilation of LDL by experimental tumours in mice.

We have studied the uptake of 125I-labelled low-density lipoprotein (LDL) by seven experimental murine tumours in vivo. Four tumours (Lewis Lung carcinoma, B-16, MS-2 and Colon 26) showed a higher relative uptake of lipoprotein as compared to the liver, two (L-1210 and P-388) had a very low lipoprotein uptake, while lipoprotein uptake by tumour M5 was similar to that of the liver. The data was confirmed by tracing tissue uptake of lipoproteins using [14C]sucrose-labeled LDL. These in vivo findings correlated well with the in vitro specific binding of 125I-beta-VLDL to membranes prepared from tumours, thus suggesting that the expression of the LDL receptor in the tumours is related to the in vivo uptake of lipoprotein. Further analysis of the LDL receptor by ligand blotting showed that the tumor receptor has several of the liver LDL receptor characteristics (including apparent Mr, sensitivity to proteinases, and Ca2+ requirement of lipoprotein binding). In summary, our data show that experimental murine tumours express the LDL receptor and suggest that the high relative in vivo uptake of LDL is determined by the elevated LDL-receptor expression in the tumours.

Animals↗
PubMed1989

Toxicity of fenclor 42 in mice: effects on immunocompetent cells.

The aim of this study is to evaluate the effects of Fenclor 42 (a mixture of trichlorobiphenyls) on the immune system. A prolonged administration of this compound to CD2F1 mice resulted in a reduction of relative spleen and thymus weight according to the dose. Furthermore, spleen weights, total number of splenocytes and relative spleen weights decreased significantly also following a single treatment with 0.5 g/kg or 1 g/kg of Fenclor 42. An analysis of the functional activity of splenocytes pointed out that proliferative response to mitogens was also inhibited. Splenic parameters returned to normal values within 5 days after a single treatment and between 8 and 15 days after a subchronic administration. The functional activity of splenocytes was restored between day +5 and day +8 according to the different schedules of treatment. On the contrary, natural killer cell (NK) activity was never affected by Fenclor 42. Studies are in progress to elucidate the intimate mechanism of the toxicity of Fenclor 42 on immunocompetent cells.

Animals↗
PubMed1988

Induction of new antigenic properties on DTIC-treated L1210 clones.

In vivo treatment of mouse leukemia L1210 with DTIC can induce new antigens on tumor cells that are not detectable on parental cells and that are transmissible as a genetic character. Moreover, L1210/DTIC is rejected by syngeneic hosts. The aim of this study was to investigate whether DTIC selects pre-existing immunogenic clones rather than inducing ex novo new antigenic determinants and to verify the number of induced antigens. L1210 leukemia was cloned in vitro and 4 clones were treated in vivo with DTIC. All the treated clones displayed antigenic properties since they were rejected by syngeneic hosts. Cytotoxic T lymphocytes (CTL) activated against one DTIC clone could recognize and lyse the relevant target. One of these DTIC-modified clones (L4/DTIC) was recloned and the subclones were tested in vivo and in vitro. Two out of six subclones were rejected by syngeneic hosts. CTL specific against these two clones were able to recognize and lyse all the other clones to different degrees. The degree of susceptibility to lysis did not correlate with the capability to evoke an immune response in vivo. Based on these findings we conclude that DTIC does not select pre-existing clones but modifies the tumor cells antigenically, and that the antigenicity induced by DTIC in a cloned tumor line is due to the presence of common antigens shared to different degrees with treated cells.

Animals↗
PubMed1988

DTIC xenogenized lines obtained from an L1210 clone: clonal analysis of cytotoxic T lymphocyte reactivity.

Antineoplastic compounds can induce on tumour cells new antigens that undetectable on parental cells and which are transmissible as a genetic character. In this study mouse leukaemia L1210 was cloned in vitro by limiting dilution and one cloned line was recloned in vivo. Four subcloned tumour cell lines (A,D,R,S) were xenogenized in vivo by DTIC treatment (A/DTIC, D/DTIC, R/DTIC, S/DTIC) following a schedule previously described. Up to 10(7) cells of these xenogenized subclones, injected i.p., were rejected by syngeneic hosts, although they grew in immunosuppressed hosts. The DTIC treated subclones were lysed by in vivo-primed, in vitro-restimulated (with the relevant subclone) lymphocytes. The cytotoxic lymphocyte activity was not strictly specific since parental, DTIC-untreated cells were also lysed, although less efficiently. CTL directed against the D/DTIC subclone were cloned by limiting dilution. Ninety-four CTL clones were assayed against L1210 subcloned cells, DTIC-treated and untreated, and against different murine tumours (syngeneic or allogenic). Three specific antigens could be identified in the 51Cr release assay. The DTIC subclones expressed one antigen that was specifically recognized by a set of CTL clones. A number of CTL clones were able to lyse the L1210 subcloned cell exclusively, targetting a tumour-associated antigen that did not appear to be modified in the DTIC-treated subclones. A third antigen was demonstrated in the parental and DTIC treated D subclone. On the basis of these results it was postulated that there was at least one common DTIC-inducible antigen specific and reproducible within an identical cell population. Moreover, DTIC treatment did not modify histocompatibility antigens or TAA pre-existing in L1210 cells. The findings discussed here provide new information about permanent xenogenization of tumour cells, which might be exploited for experimental chemo-immunotherapy of cancer.

Animals↗
PubMed1988

Further evidence that brain histamine H2 receptors are stimulatory in the control of prolactin in the rat.

The effects of administration into the brain ventricle of H2 receptor agonists (4-methylhistamine, 0.8 mumol/rat; dimaprit, 0.4-0.8 mumol/rat), H2 antagonists (cimetidine, 0.8 mumol/rat; ranitidine, 0.4-0.8 mumol/rat; famotidine, 0.03 mumol/rat) and of the dimaprit chemical analogue SK&F 91487 (0.4 mumol/rat) on unstimulated and histamine-stimulated prolactin secretion in normal male rats were studied. The H2 agonist 4-methylhistamine caused a significant increase in unstimulated blood PRL, whereas dimaprit, SK&F 91487, and the H2 antagonists tested did not change PRL levels. 4-Methylhistamine significantly enhanced the stimulatory effects of histamine on prolactin, whereas all the H2 antagonists inhibited histamine-induced prolactin release. The inhibition of histamine-induced prolactin secretion by the H2 agonist dimaprit is nonspecific, since its chemical analogue SK&F 91487, which has no H2 agonist activity, also inhibits it. These results indicate that stimulation of the H2 receptors in the central nervous system is facilitatory for PRL secretion, suggesting that the activation of H2 receptors may contribute to the PRL-releasing effects of histamine.

Animals↗
PubMed1987

Adoptive immunity in mice challenged with L1210/DTIC clones.

New antigenic specificities, not detectable on parental cells, have been induced by many investigators in mouse lymphomas by treatment with the antitumor agent 5(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). The antigens are transmissible, after withdrawal of the drug treatment, as an inheritable character. The mechanism of induction, the molecular nature, and the number of the new antigenic specificities have not been completely elucidated. Four clones from murine leukemia L1210 isolated and expanded in vitro were treated in vivo with DTIC and the new sublines were studied in detail. The four drug-treated sublines studied exhibited strong immunogenicity since they were rejected by syngeneic animals. Immunosuppressed animals challenged with 10(7) A/DTIC or P/DTIC cells were reciprocally protected by the adoptive transfer of spleen cells from donors that had rejected a lethal challenge of A/DTIC or P/DTIC clone. In a similar fashion, the adoptive transfer of spleen cells obtained from animals that had rejected the Q/DTIC or the R/DTIC clones protected immunosuppressed mice challenged with Q/DTIC or R/DTIC cells. No antitumor activity was observed in cross-protective schedules other than those indicated. It was been concluded that (a) the L1210 leukemia line does not have antigenic cells, (b) four DTIC-treated clone sublines were rejected by compatible hosts, and (c) two mutually exclusive sets of antigens were expressed in four antigenic clone sublines.

Animals↗
PubMed1987

Photodynamic therapy in vitro and in vivo with hematoporphyrin derivative and laser light.

Photodynamic therapy is currently under investigation as a new form of treatment for solid malignant tumors in animals and in humans. The method involves photosensitization of drugs and fluorescent dyes, such as hematoporphyrin derivative (Hpd), after preferential incorporation by neoplastic cells. In in vitro experiments laser light activation completely destroys Hpd-pretreated EL4 cells. Mice bearing MS-2 fibrosarcoma treated with Hpd and laser light survived indefinitely, in comparison with control animals that were untreated or treated only with Hpd or laser light. In mice bearing the highly metastatic tumors B16 melanoma and Lewis lung carcinoma (LLC) treated with Hpd and laser light delivered through a quartz fiber optic significantly prolonged the median survival time. This therapy was compared with surgical excision of primary tumors and, for superficial nonmetastatic neoplasma MS-2, the photodynamic therapy was more effective than surgery, while for metastatic tumors B16 and LLC, there was no significant difference between the two methodologies. However, phototherapy is much less traumatic to the animals.

Animals↗
PubMed1986

L1210/DTIC antigenic subline: studies at the clone level.

Treatment of murine tumors with the anti-tumor agent 5-(3,3 dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) has resulted in the induction of antigenic specificities not found in parental cells. After the withdrawal of DTIC treatment, the antigenic sublines maintained the new properties indefinitely, as a heritable character although the mechanism of induction and the molecular nature of the new antigens are essentially unknown. Seven clones from the murine immunogenic leukemia L1210/DTIC were selected and studied in some detail. Three of the seven clones showed an increased immunogenicity in vivo since two clones (D5 and D7) were rejected by syngenic mice and one (D6) prolonged the life span for 3 weeks (untreated tumours killed the mice in 7 days). The seven clones and the L1210/DTIC were recognized and lysed by in vivo primed, in vitro stimulated (with L1210/DTIC) lymphocytes. Therefore, the seven clones shared antigens with the L1210-DTIC immunogenic subline. Secondary stimulated lymphocytes to clone D5, and clone D7 were able to lyse D5, D6 and D7 cells, respectively, but were unable to recognize the remaining clones. From in vivo and in vitro studies, all the L1210/DTIC sublines are composed of cells carrying two or more distinct antigens. Each cell clone expressed one set of antigens. It was concluded that only a few antigens expressed in different cells were induced by a DTIC treatment of L1210 leukemia.

Animals↗
PubMed1985

The bone scan in patients with aluminium-associated bone disease.

The bone scans of 32 patients on regular dialysis who received desferrioxamine therapy for fracturing osteomalacia secondary to aluminium intoxication are reviewed. All scans show the same pattern, with lack of tracer deposition in bone and deposition in soft tissues. Therapy with desferrioxamine controlled the aluminium intoxication in all cases, and in 21 patients the bone scan reverted to normal or showed a pattern typical of hyperparathyroidism.

Aluminum↗
PubMed1984

Hematoporphyrin derivative rescue from toxicity caused by chemotherapy or radiation in a murine leukemia model (L1210).

Hematoporphyrin [1,3,5,8-tetramethyl-2,4-bis(hydroxyethyl)-porphin-6,7-dipropio nic acid dihydrochloride derivative] (HPD) is a compound that was studied in a number of laboratories because of its cytocidal activity after activation by light. Modification of immune function seen during the photochemotherapeutic studies prompted attempts to determine the effect of HPD on the immune and hemopoietic systems. Splenic hyperplasia as well as marrow hypercellularity were noted in mice treated with HPD. In vitro phytohemagglutinin or lipopolysaccharide stimulation of spleen lymphocytes caused normal or scant increases in blast transformation compared to the stimulation index for lymphocytes from untreated animals. HPD treatment did not significantly alter production of antibody to sheep red blood cells, as evaluated by hemagglutination or hemolytic assay. In contrast, HPD treatment did promote an increased number of spleen colonies in lethally irradiated mice transfused with syngeneic bone marrow. The capacity of HPD to increase the number of bone marrow and spleen cells has been exploited to accelerate the recovery from peripheral leukopenia induced in animals by previous drug or radiation treatment. The time for full return from severe leukopenia induced by an antimetabolite compound (5-fluorouracil) or an alkylating agent (cyclophosphamide or X-rays was significantly shorter in mice treated with HPD than in controls. Furthermore, improved survival was demonstrated in irradiated mice after HPD treatment. Finally, HPD treatment of L1210 leukemic mice did not affect the antitumor activity of cyclophosphamide. If the properties described here be confirmed, HPD might contribute to recovery of leukopenic cancer patients.

Animals↗
PubMed1983

[Possible applications of living BCG and the BCG cell wall in immunotherapy].

BCG, Bacillus Calmette-Guerin, has an immunostimulant capacity and antitumor activity against both experimental and human tumors. Its mechanism of action has not yet been well clarified; maybe it involves one or more immune cell populations: in fact BCG has been reported to loose its activity in immunosuppressed animals. A limiting factor for systemic use of living BCG is its high toxicity: therefore BCG-derivatives have been introduced in both the experimental and the clinical fields. For experimental use one of the most interesting of these products is BCG-cell wall: when used in laboratory animals it demonstrated an efficient dose-dependent antitumor activity and lack of toxicity. On the contrary living BCG was notably toxic and ineffective when used in high doses. An interesting approach in antineoplastic therapy is the use of BCG with tumor cells as a vaccine against micrometastases remaining after surgery, chemotherapy or radiotherapy. A vaccine containing BCG-cell wall and tumor cells (either living or x-irradiated) gave very encouraging experimental results for a possible clinical use in the treatment of tumor metastases.

BCG Vaccine↗
PubMed1983

In vitro hematoporphyrin (Hpd) inhibitory effects on some immunological assays.

Hematoporphyrin derivative (Hpd) is a fluorescent dye that is preferentially incorporated by tissues with a high mitotic index, such as tumor cells and blast cells. A cytotoxic effect is produced following light activation. Previous studies have shown a long lasting reversible inhibition of DNA synthesis in Hpd-treated cells that failed to stimulate allogeneic lymphocytes in either primary or in secondary MLR. In this study we report Hpd inhibitory effects on some immunological assays in vitro. Treatment with Hpd of cytotoxic effector cells resulted in inhibition of their lytic activity likely dependent on the loss of binding to target cells. In the same way Hpd treatment inactivated the lytic activity of NK cells. In contrast Hpd-treatment of target cells did not modify the above immunological reactions. Moreover Con A agglutinability, antibody dependent capping as well as E-rosettes were inhibited following an Hpd treatment of relevant cells. Since normal susceptibility to humoral and cell mediated lysis was exhibited by Hpd-treated cells it is unlikely that cell surface molecules were damaged. An inhibitory effect exerted by an Hpd treatment on cell surface movements might explain these findings.

Agglutination↗